Efficient asymmetric synthesis of 1-cyano-tetrahydroisoquinolines from lipase dual activity and opposite enantioselectivities in α-Aminonitrile resolution.

Dual promiscuous racemization/amidation activities of lipases leading to efficient dynamic kinetic resolution protocols of racemic α-aminonitrile compounds are described. α-Amidonitrile products of high enantiomeric purity could be formed in high yields. Several lipases from different sources were shown to exhibit the dual catalytic activities, where opposite enantioselectivities could be recorded for certain substrates.

Asymmetric Synthesis of Substituted Thiolanes through Domino Thia-Michael-Henry Dynamic Covalent Systemic Resolution using Lipase Catalysis.

Dynamic systems based on consecutive thia-Michael and Henry reactions were generated and transformed using lipase-catalyzed asymmetric transformation. Substituted thiolane structures with three contiguous stereocenters were resolved in the process in high yields and high enantiomeric excesses.

In situ evaluation of lipase performances through dynamic asymmetric cyanohydrin resolution.

A dynamic resolution process based on multiple reversible cyanohydrin formation coupled to lipase-mediated transesterification is demonstrated. The resulting process resulted in the efficient evaluation of complex lipase performances in asymmetric cyanohydrin acylate synthesis. Dynamic systems were generated and resolved in situ, and the effects of the reaction conditions could be directly monitored for the overall system. By this concept, the enzyme activity, chemo- and stereoselectivity for all involved substrates could be simultaneously evaluated.

Dynamic asymmetric multicomponent resolution: lipase-mediated amidation of a double dynamic covalent system.

The Strecker reaction is one of the most important multicomponent reactions developed, leading to alpha-aminonitriles that are versatile substrates for many synthetic applications. In the present study, this reaction type has been applied to a double dynamic covalent resolution protocol, leading to efficient C-C- and C-N-bond generation as well as chiral discrimination. The combination of transimination with imine-cyanation enabled the dynamic exchange in more than one direction around a single stereogenic center of restricted structure. This multiple exchange process could generate a vast range of compounds from a low number of starting materials in very short time. The resulting double dynamic covalent systems, created under thermodynamic control, were subsequently coupled in a one-pot process with kinetically controlled lipase-mediated transacylation. This resulted in complete resolution of the dynamic systems, yielding the optimal N-acyl-alpha-aminonitriles for the enzyme, where the individual chemoenzymatic reactions could produce enantiomerically pure acylated N-substituted alpha-aminonitriles in good yields.

Phosphine-catalyzed disulfide metathesis.

The reaction between disulfides and phosphines generates a reversible disulfide metathesis process.

Tandem driven dynamic combinatorial resolution via Henry-iminolactone rearrangement.

An unexplored type of tandem reaction is used to kinetically resolve a dynamic combinatorial library resulting in quantitative amplification of an interesting 3-substituted isoindolinone,

Ketene acetal and spiroacetal constituents of the marine fungus Aigialus parvus BCC 5311.

Aigialone (1) and aigialospirol (2), two structurally unique compounds, were isolated from the mangrove fungus Aigialus parvus BCC 5311. The structure of the new ketene acetal 1 was elucidated by spectral analysis, and its relative stereochemistry was determined by X-ray crystallography. The stereochemistry of aigialospirol (2), elucidated by NMR spectral analysis, suggested that this compound is possibly derived from hypothemycin (3), a metabolite previously isolated from this same fungus.